Angiotensinogen and Megalin Interactions Contribute to Atherosclerosis-Brief Report.
Angiotensin II
/ biosynthesis
Angiotensinogen
/ physiology
Animals
Atherosclerosis
/ etiology
Female
Hypercholesterolemia
/ complications
Low Density Lipoprotein Receptor-Related Protein-2
/ antagonists & inhibitors
Male
Mice
Mice, Inbred C57BL
Oligonucleotides, Antisense
/ pharmacology
Renin-Angiotensin System
/ physiology
angiotensinogen
angiotensins
atherosclerosis
mice
renin
Journal
Arteriosclerosis, thrombosis, and vascular biology
ISSN: 1524-4636
Titre abrégé: Arterioscler Thromb Vasc Biol
Pays: United States
ID NLM: 9505803
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
pubmed:
21
12
2018
medline:
4
12
2019
entrez:
21
12
2018
Statut:
ppublish
Résumé
Objective- AGT (Angiotensinogen) is the unique precursor of the renin-angiotensin system that is sequentially cleaved by renin and ACE (angiotensin-converting enzyme) to produce Ang II (angiotensin II). In this study, we determined how these renin-angiotensin components interact with megalin in kidney to promote atherosclerosis. Approach and Results- AGT, renin, ACE, and megalin were present in the renal proximal convoluted tubules of wild-type mice. Hepatocyte-specific AGT deficiency abolished AGT protein accumulation in proximal tubules and diminished Ang II concentrations in kidney, while renin was increased. Megalin was most abundant in kidney and exclusively present on the apical side of proximal tubules. Inhibition of megalin by antisense oligonucleotides (ASOs) led to ablation of AGT and renin proteins in proximal tubules, while leading to striking increases of urine AGT and renin concentrations, and 70% reduction of renal Ang II concentrations. However, plasma Ang II concentrations were unaffected. To determine whether AGT and megalin interaction contributes to atherosclerosis, we used both male and female low-density lipoprotein receptor
Identifiants
pubmed: 30567480
doi: 10.1161/ATVBAHA.118.311817
pmc: PMC6344256
mid: NIHMS1516517
doi:
Substances chimiques
Low Density Lipoprotein Receptor-Related Protein-2
0
Lrp2 protein, mouse
0
Oligonucleotides, Antisense
0
Angiotensinogen
11002-13-4
Angiotensin II
11128-99-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
150-155Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL139748
Pays : United States
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